DESCRIPTION: (Applicant's Description) There is no doubt that cigarette smoking is a substantial source of morbidity and premature morbidity the United States. Each year, cigarette smoking causes about 30 to 40 percent of coronary heart disease deaths and 30 percent of cancer deaths, leading to nearly half a million deaths each year. Yet, despite these statistics, there are more than 54 million smokers in the nation. Four million of these are adolescents and over 3,000 youth start smoking each day. If these rates of teenage smoking continue, the costs to society will be enormous. Cigarette smoking has become so widespread in youth that it is considered a "pediatric disease" by the Food and Drug Administration. Studies suggest that most adults could be prevented from becoming tobacco users if they could be kept tobacco-free during adolescence. This finding suggests that preventive efforts focus on adolescence, a known risk period for the initiation of smoking. This proposal seeks to apply a psychopharmacologic high risk paradigm to prevent regular smoking and nicotine dependence in adolescence. The work has three innovative features: 1) use of epidemiologic data to define a group of adolescents at high risk for smoking; 2) use of an anti-smoking medication that also addresses clinical features of the high-risk group and 3) implementation of procedure to facilitate the long-term follow-up of research participants. These features are defined by the three main aims of our proposal. Prior work shows that children with attention deficit hyperactivity disorder (ADHD), who also have comorbid conduct, mood or anxiety disorders, are at high risk for regular smoking and nicotine dependence. Thus, our first aim is to recruit a group of these adolescents into a preventative treatment protocol, before they have initiated regular smoking. Our second aim is to complete a double-blind clinical trial of bupropion for the prevention of smoking in high-risk ADHD adolescents. Bupropion is an appropriate agent for this group for several reasons. It is efficacious for the treatment of depression, one of the most common comorbid disorders in the high risk group. Moreover, prior research also shows that it reduces ADHD symptoms and is an effective treatment for smoking cessation. Moreover, its putative mechanism of action affects neural systems believed to mediate both ADHD and smoking. In addition to these main aims, we will assess the effects of bupropion on symptoms of ADHD and depression and will implement procedures that will allow us to study the outcome of this sample in future proposals, should that be warranted. We will use a balanced, double-blind, placebo-controlled study design. Sixty-five high risk adolescents will be given placebo and sixty-five bupropion. Subjects will he recruited over a 3-month period and will have varying lengths of follow-up based on when they were recruited into the study. The study is designed so that each subject will have at least one year of follow-up data. Some subjects will have as much as 3.5 years of follow-up data. The use of pharmacological agents, such as Bupropion, have not been explored in the prevention of cigarette smoking. Since this medication has been used for both the treatment of ADHD and cigarette smoking, it could aid in the prevention of cigarette smoking in this high-risk population. The number of cases that could he prevented is not trivial. Since there are estimated to be 3.5 million children with ADHD and 20% have been shown to be smokers, targeting this group could potentially impact 700,000 children and adolescents.